Diabetes mellitus type 2 (also referred to as noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes) is a metabolic disorder that is characterized by high blood glucose in the presence of insulin resistance and relative insulin deficiency. Type 2 diabetes is a progressive disease in which the risks of myocardial infarction, stroke, microvascular events and mortality are all strongly associated with hyperglycaemia. Type 2 diabetes is also a silent disease with significant declines in β-cell function and kidney damage often occurring before any symptoms of the disease manifest.
The progression from normal glucose tolerance (NGT) to type 2 diabetes involves intermediate stages of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), also known as prediabetes. The pathophysiology underlying the development of these glucose metabolic alterations is multifactorial and includes, for example, lifestyle and genetic factors. In particular, obesity is thought to be the primary cause of type 2 diabetes in people who are genetically predisposed to the disease and rates of type 2 diabetes have increased markedly over the last 50 years in parallel with obesity. As of 2010 there are approximately 285 million people with the disease compared to around 30 million in 1985.
Although numerous risk factors, such as age, body mass index (BMI), and ethnicity, have been associated with the development of prediabetes and type 2 diabetes, these are not adequate to accurately predict the risk of progression from normal glucose tolerance to impaired glucose tolerance and/or from impaired glucose tolerance to type 2 diabetes since the development and progression of diabetes is often silent with organ damage occurring before the onset of identifiable symptoms. In addition, although methods for determining whether a subject has impaired glucose tolerance and/or type 2 diabetes are known (e.g., glucose tolerance testing), such methods require overnight fasting and multiple blood draws over several hours and are often associated with side effects, such as, nausea, vomiting, abdominal bloating, and/or headache.
Accordingly, as early identification of subjects who have impaired glucose tolerance and/or type 2 diabetes and/or who are at risk of developing impaired glucose tolerance and/or type 2 diabetes and/or those that will respond to a particular therapy would decrease short-term and long-term complications associated with glucose imbalance, there is a need in the art for reliable and accurate methods of determining which subjects have or will develop impaired glucose tolerance and/or type 2 diabetes and/or respond to a therapy to permit early intervention.